The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times (>12 h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.

Abstract Various factors in the tumor microenvironment (TME) regulate the expression of PD-L1 in carcinoma cells. The cancer-associated fibroblasts (CAFs) play a crucial role in regulating and rewiring TME to enhance their immune suppressive function and to favor the invasion of the malignant cells. Tumor progression may be retarded by targeting CAFs in the TME. Various studies highlighted the ability of targeting CAF with pirfenidone (PFD), leading to increased efficacy of chemotherapy. However, its potential for the reduction of immune-suppression capacity of CAFs remains to be elusive. Here, we assessed the effect of PFD on the expression of PD-L1 on CAF cells. Besides migration inhibitory effects of PFD on CAFs, the expression level of PD-L1 reduced in CAFs after treatment with PFD. The downstream analysis of released cytokines from CAFs showed that PFD significantly dropped the secretion of CCL17 and TNF-β, where a positive association between PFD-targeted proteins and PD-L1 was observed. These data suggest that the treatment of CAF within TME through the PFD may reduce the acquisition of CAF-mediated invasive and immune-suppressive capacity of breast carcinoma cells.

The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2’s molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.

Mutations of HBsAg especially within the "a" determinant could alter the antigenicity of the protein causing failure of HBsAg neutralization and escaping from the host's immune system, resulting in active viral replication and liver disease. This project aimed to investigate mutation in the S gene region of HBV infected patients in Golestan Province-Iran. HBV-DNA extractions from plasma and PCR of 100 patients were performed. Direct sequencing and alignment of S gene were applied using reference sequence from Gene Bank database. All isolates were belonged to genotype D, subgenotype D1, subtype ayw2. Overall 92 point mutations occurred. Of them, 40 (43.47%) were missense and 52 (56.52%) were silent. Mutations were detected in 95 cases (95%). Five of 40 mutations (12.5%) occurred in "a" determinant and 13 (32.5%), 17 (42.5%), and 2 (5%) were seen in antigenic epitope regions of B cell, CD 4 + and CTL, respectively. Frame shift mutations were seen in 22 cases (22%). 14% of mutations occurred at Major Hydrophilic Region(MHR) area which P120T/S and R122K/T substitutions were the most frequent ones (4%). Mutation in G145R of the S gene was observed in one case. A large number of MHR mutants are in association with failure of HBsAg detection, vaccine, and immunotherapy escape. This study showed "a" determinant S gene mutations in HBV infected people with HBsAg positivity in Golestan Province-Iran. The rate of mutation in our study was 95%. Collectively, the results of this project exhibited that most of mutations were clustered in CD 4 + antigenic epitopes. © Springer Science+Business Media, LLC 2012